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A Study of Neoadjuvant Atezolizumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Patients With Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer (IMpower030)

Registration Number
NCT03456063
Lead Sponsor
Hoffmann-La Roche
Brief Summary

This is a randomized, double-blinded study designed to evaluate the efficacy, safety, pharmacokinetics, and immunogenicity of neoadjuvant treatment with atezolizumab (MPDL3280A) or placebo in combination with platinum-based chemotherapy in participants with resectable Stage II, IIIA, or select IIIB non-small cell lung cancer (NSCLC) followed by open-label adjuvant/postoperative atezolizumab or best supportive care and monitoring.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
453
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm A: Atezolizumab + platinum-based chemotherapyAtezolizumab (MPDL3280A), an engineered anti-PD-L1 antibodyNeoadjuvant treatment will consist of 4 cycles; atezolizumab + platinum-based chemotherapy Platinum-based chemotherapy may include: * carboplatin + pemetrexed * carboplatin + nab-paclitaxel * cisplatin + pemetrexed * cisplatin + gemcitabine Post-operative adjuvant treatment will consist of 16-cycles of atezolizumab
Arm A: Atezolizumab + platinum-based chemotherapyNab-paclitaxelNeoadjuvant treatment will consist of 4 cycles; atezolizumab + platinum-based chemotherapy Platinum-based chemotherapy may include: * carboplatin + pemetrexed * carboplatin + nab-paclitaxel * cisplatin + pemetrexed * cisplatin + gemcitabine Post-operative adjuvant treatment will consist of 16-cycles of atezolizumab
Arm B: Placebo + platinum-based chemotherapyCisplatinNeoadjuvant treatment will consist of 4 cycles; placebo + platinum-based chemotherapy Platinum-based chemotherapy may include: * carboplatin + pemetrexed * carboplatin + nab-paclitaxel * cisplatin + pemetrexed * cisplatin + gemcitabine Participants will receive best supportive care and monitoring after surgery
Arm B: Placebo + platinum-based chemotherapyPlacebo ComparatorNeoadjuvant treatment will consist of 4 cycles; placebo + platinum-based chemotherapy Platinum-based chemotherapy may include: * carboplatin + pemetrexed * carboplatin + nab-paclitaxel * cisplatin + pemetrexed * cisplatin + gemcitabine Participants will receive best supportive care and monitoring after surgery
Arm B: Placebo + platinum-based chemotherapyNab-paclitaxelNeoadjuvant treatment will consist of 4 cycles; placebo + platinum-based chemotherapy Platinum-based chemotherapy may include: * carboplatin + pemetrexed * carboplatin + nab-paclitaxel * cisplatin + pemetrexed * cisplatin + gemcitabine Participants will receive best supportive care and monitoring after surgery
Arm B: Placebo + platinum-based chemotherapyPemetrexedNeoadjuvant treatment will consist of 4 cycles; placebo + platinum-based chemotherapy Platinum-based chemotherapy may include: * carboplatin + pemetrexed * carboplatin + nab-paclitaxel * cisplatin + pemetrexed * cisplatin + gemcitabine Participants will receive best supportive care and monitoring after surgery
Arm A: Atezolizumab + platinum-based chemotherapyCarboplatinNeoadjuvant treatment will consist of 4 cycles; atezolizumab + platinum-based chemotherapy Platinum-based chemotherapy may include: * carboplatin + pemetrexed * carboplatin + nab-paclitaxel * cisplatin + pemetrexed * cisplatin + gemcitabine Post-operative adjuvant treatment will consist of 16-cycles of atezolizumab
Arm A: Atezolizumab + platinum-based chemotherapyCisplatinNeoadjuvant treatment will consist of 4 cycles; atezolizumab + platinum-based chemotherapy Platinum-based chemotherapy may include: * carboplatin + pemetrexed * carboplatin + nab-paclitaxel * cisplatin + pemetrexed * cisplatin + gemcitabine Post-operative adjuvant treatment will consist of 16-cycles of atezolizumab
Arm A: Atezolizumab + platinum-based chemotherapyGemcitabineNeoadjuvant treatment will consist of 4 cycles; atezolizumab + platinum-based chemotherapy Platinum-based chemotherapy may include: * carboplatin + pemetrexed * carboplatin + nab-paclitaxel * cisplatin + pemetrexed * cisplatin + gemcitabine Post-operative adjuvant treatment will consist of 16-cycles of atezolizumab
Arm A: Atezolizumab + platinum-based chemotherapyPemetrexedNeoadjuvant treatment will consist of 4 cycles; atezolizumab + platinum-based chemotherapy Platinum-based chemotherapy may include: * carboplatin + pemetrexed * carboplatin + nab-paclitaxel * cisplatin + pemetrexed * cisplatin + gemcitabine Post-operative adjuvant treatment will consist of 16-cycles of atezolizumab
Arm B: Placebo + platinum-based chemotherapyCarboplatinNeoadjuvant treatment will consist of 4 cycles; placebo + platinum-based chemotherapy Platinum-based chemotherapy may include: * carboplatin + pemetrexed * carboplatin + nab-paclitaxel * cisplatin + pemetrexed * cisplatin + gemcitabine Participants will receive best supportive care and monitoring after surgery
Arm B: Placebo + platinum-based chemotherapyGemcitabineNeoadjuvant treatment will consist of 4 cycles; placebo + platinum-based chemotherapy Platinum-based chemotherapy may include: * carboplatin + pemetrexed * carboplatin + nab-paclitaxel * cisplatin + pemetrexed * cisplatin + gemcitabine Participants will receive best supportive care and monitoring after surgery
Primary Outcome Measures
NameTimeMethod
Independent Review Facility (IRF)-Assessed Event Free Survival (EFS)Up to approximately 96 months

IRF-assessed EFS is defined as the time from randomization to the first documented disease progression per RECIST v1.1 that precludes surgery, local or distant disease recurrence, or death from any cause, whichever occurs first.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With Adverse Events (AEs)Up to approximately 96 months
Objective Response (OR)Prior to surgery, up to approximately 84 days

Objective response is defined as a complete response or partial response, as determined by the investigator according to RECIST v1.1

Length of Surgical DelaysUp to approximately 96 months

Length of surgical delays.

Investigator-Assessed EFSUp to approximately 96 months

EFS is defined as the time from randomization to the first documented disease progression per RECIST v1.1 that precludes surgery, local or distant disease recurrence, as assessed by the investigator; or death from any cause, whichever occurs first.

2-Year and 3-Year OSUp to approximately 96 months

The 2-year and 3-year OS rate is defined as the probability that a participant will be alive 2 years and 3 years after randomization, respectively.

Change from baseline in HRQoL scoresUp to approximately 96 months

Change from baseline in HRQoL scores as assessed through use of the two-item GHS/HRQoL subscale (Questions 29 and 30) of the EORTC QLQ-C30 at each assessment time point during the study through the completion of adjuvant treatment and observation follow-up assessments

Number and Severity of Surgical Related Adverse EventsUp to approximately 96 months
Number of Surgical DelaysUp to approximately 96 months

Number of surgical delays.

Maximum Observed Serum Atezolizumab Concentration (Cmax)Pre-dose on Day 1 of Cycles 1 and 3 for Neoadjuvant Treatment; Pre-dose on Day 1 of Cycles 5, 7, 9, 11 and 19 for Arm A. Each cycle is 21 days; at treatment or observation follow-up discontinuation (up to approximately 96 months)

Cmax is the maximum (or peak) concentration that a study drug achieves in the body.

Pathological Complete Response (pCR)At time of surgery

pCR is defined as the absence of any viable primary tumor cells at the time of surgical resection in the primary tumor and all sampled lymph nodes as assessed by central and local pathology laboratory.

Major Pathological Response (MPR)At time of surgery

MPR is defined as ≤ 10% residual viable tumor cells at the time of surgical resection in the primary tumor, as assessed by central and local pathology laboratory.

Overall Survival (OS)Up to approximately 96 months

OS is defined as the time from randomization to death from any cause during the course of the study.

Disease-Free Survival (DFS)Up to approximately 96 months

DFS is defined as the time from the first date of no disease to local or distant recurrence (including occurrence of new primary NSCLC) or death due to any cause, whichever occurs first, as determined by the investigator during the adjuvant treatment and observation follow-up

2-Year and 3-Year Independent Review Facility-Assessed EFSUp to approximately 96 months

EFS is defined as the probability that a participant will be event-free 2 years and 3 years after randomization, respectively, as assessed by the Independent Review Facility.

2-Year and 3-Year Investigator-Assessed EFSUp to approximately 96 months

EFS is defined as the probability that a participant will be event-free 2 years and 3 years after randomization, respectively, as assessed by the Investigator.

Number of Operative and Post-Operative ComplicationsUp to approximately 96 months

Number of operative and post-operative complications.

Reasons for Surgical CancellationsUp to approximately 96 months

Reasons for surgical cancellations.

Minimum Observed Serum Atezolizumab Concentration (Cmin)Pre-dose on Day 1 of Cycles 1 and 3 (each cylce is 21 days) for Neoadjuvant Treatment; pre-dose on Day 1 of Cycles 5, 7, 9, 11 and 19 (each cycle is 21 days) for Arm A; at treatment or observation follow-up discontinuation (up to approximately 96 months)

Cmin is the minimum (or trough) concentration that a study drug achieves in the body.

Percentage of Participants With Anti-Drug Antibody (ADA) to AtezolizumabPre-dose on Day 1 of Cycles 1 and 3 for Neoadjuvant Treatment; Pre-dose on Day 1 of Cycles 5, 7, 9, 11 and 19 for Arm A. Each cycle is 21 days; at treatment or observation follow-up discontinuation (up to approximately 96 months)

Trial Locations

Locations (116)

Hospital Clinico San Carlos

🇪🇸

Madrid, Spain

Hospital Regional Universitario Carlos Haya

🇪🇸

Malaga, Spain

Hospital Universitario Virgen Macarena

🇪🇸

Sevilla, Spain

Hospital Clinico Universitario de Valencia

🇪🇸

Valencia, Spain

Barts and the London NHS Trust.

🇬🇧

London, United Kingdom

Sendai Kousei Hospital

🇯🇵

Miyagi, Japan

Okayama University Hospital

🇯🇵

Okayama, Japan

Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital

🇯🇵

Tokyo, Japan

Arizona Oncology

🇺🇸

Tucson, Arizona, United States

USC Norris Cancer Center

🇺🇸

Los Angeles, California, United States

The Center for Cancer Prevention and Treatment at St.Joseph Hospital of Orange

🇺🇸

Orange, California, United States

UC Davis Cancer Center

🇺🇸

Sacramento, California, United States

Scripps Clinic

🇺🇸

San Diego, California, United States

National Jewish Health

🇺🇸

Denver, Colorado, United States

Rocky Mountain Cancer Center

🇺🇸

Denver, Colorado, United States

Georgetown University

🇺🇸

Washington, District of Columbia, United States

Washington Cancer Institute

🇺🇸

Washington, District of Columbia, United States

Illinois Cancer Care

🇺🇸

Peoria, Illinois, United States

Uni of Maryland Cancer Center

🇺🇸

Baltimore, Maryland, United States

University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

Brighton Center for Specialty Care

🇺🇸

Brighton, Michigan, United States

Barbara Ann Karmanos Cancer Institute

🇺🇸

Detroit, Michigan, United States

Minnesota Oncology Minneapolis

🇺🇸

Minneapolis, Minnesota, United States

Mayo Clinic - Rochester

🇺🇸

Rochester, Minnesota, United States

Mercy Clinic Cancer & Hematology

🇺🇸

Springfield, Missouri, United States

Nebraska Methodist Estabrook Cancer Center

🇺🇸

Omaha, Nebraska, United States

Northwell Health

🇺🇸

Lake Success, New York, United States

NYU Winthrop Hospital

🇺🇸

Mineola, New York, United States

NYU Langone Medical Center

🇺🇸

New York, New York, United States

Columbia University Medical Center

🇺🇸

New York, New York, United States

Levine Cancer Institute

🇺🇸

Charlotte, North Carolina, United States

Lehigh Valley Health Network

🇺🇸

Allentown, Pennsylvania, United States

Sarah Cannon Research Institute / Tennessee Oncology

🇺🇸

Nashville, Tennessee, United States

Texas Oncology - South Austin

🇺🇸

Austin, Texas, United States

UT Health East Texas HOPE Cancer Center

🇺🇸

Tyler, Texas, United States

Virginia Cancer Specialists, PC

🇺🇸

Fairfax, Virginia, United States

Northwest Cancer Specialists - Vancouver

🇺🇸

Vancouver, Washington, United States

St George Hospital

🇦🇺

Kogarah, New South Wales, Australia

Box Hill Hospital

🇦🇺

Box Hill, Victoria, Australia

Peter MacCallum Cancer Center

🇦🇺

Melbourne, Victoria, Australia

Kepler Universitätskliniken GmbH - Med Campus III

🇦🇹

Linz, Austria

Ordensklinikum Linz Elisabethinen

🇦🇹

Linz, Austria

Klinik Penzing

🇦🇹

Wien, Austria

Krankenhaus Nord - Klinik Floridsdorf

🇦🇹

Wien, Austria

Cenantron - Centro Avancado de Tratamento Oncologico

🇧🇷

Belo Horizonte, Minas Gerais, Brazil

Hospital Nossa Senhora da Conceicao

🇧🇷

Porto Alegre, Rio Grande Do Sul, Brazil

Instituto do Cancer do Estado de Sao Paulo - ICESP

🇧🇷

Sao Paulo, São Paulo, Brazil

Shanghai Chest Hospital

🇨🇳

Shanghai, China

CHU Angers

🇫🇷

Angers, France

Centre Léon Bérard

🇫🇷

Lyon, France

Centre Hospitalier Saint Quentin

🇫🇷

Saint Quentin, France

Hopital d'Instruction des Armees de Begin

🇫🇷

Saint-Mande, France

CHU Strasbourg - Nouvel Hopital Civil

🇫🇷

Strasbourg, France

Hôpital d'Instruction des Armées de Sainte Anne

🇫🇷

Toulon, France

Universitätsklinikum Freiburg

🇩🇪

Freiburg, Germany

Asklepios-Fachkliniken Muenchen-Gauting

🇩🇪

Gauting, Germany

Krankenhaus Martha-Maria Halle-Doelau gGmbH

🇩🇪

Halle, Germany

Pius-Hospital Oldenburg

🇩🇪

Oldenburg, Germany

Klinikum der Univer Regenburg

🇩🇪

Regensburg, Germany

Robert Bosch Krankenhaus

🇩🇪

Stuttgart, Germany

Missionsärztliche Klinik, Gemeinnützige Gesellschaft mbH

🇩🇪

Würzburg, Germany

Semmelweis Egyetem X

🇭🇺

Budapest, Hungary

Soroka Medical Center

🇮🇱

Beer Sheva, Israel

Rambam Health Care Campus

🇮🇱

Haifa, Israel

Meir Medical Center

🇮🇱

Kfar-Saba, Israel

Sourasky / Ichilov Hospital

🇮🇱

Tel Aviv, Israel

Policlinico Universitario Campus Biomedico

🇮🇹

Roma, Lazio, Italy

Irccs Istituto Nazionale Dei Tumori (Int)

🇮🇹

Milano, Lombardia, Italy

Irccs Istituto Europeo Di Oncologia (IEO)

🇮🇹

Milano, Lombardia, Italy

A.O. Universitaria Pisana-Ospedale Cisanello

🇮🇹

Pisa, Toscana, Italy

IOV - Istituto Oncologico Veneto - IRCCS

🇮🇹

Padova, Veneto, Italy

National Hospital Organization Kyushu Cancer Center

🇯🇵

Fukuoka, Japan

Hiroshima City Hiroshima Citizens Hospital

🇯🇵

Hiroshima, Japan

Hiroshima University Hospital

🇯🇵

Hiroshima, Japan

Kobe University Hospital

🇯🇵

Hyogo, Japan

Hyogo Medical University Hospital

🇯🇵

Hyogo, Japan

Kyoto University Hospital

🇯🇵

Kyoto, Japan

Fukushima Medical University Hospital

🇯🇵

Miyagi, Japan

Kurashiki Central Hospital

🇯🇵

Okayama, Japan

Osaka City General Hospital

🇯🇵

Osaka, Japan

Osaka International Cancer Institute

🇯🇵

Osaka, Japan

The Cancer Institute Hospital of JFCR

🇯🇵

Tokyo, Japan

Tokyo Medical University Hospital

🇯🇵

Tokyo, Japan

Kosin University Gospel Hospital

🇰🇷

Busan, Korea, Republic of

St. Vincent's Hospital

🇰🇷

Gyeonggi-do, Korea, Republic of

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Gangnam Severance Hospital

🇰🇷

Seoul, Korea, Republic of

Korea University Guro Hospital

🇰🇷

Seoul, Korea, Republic of

Uniwersyteckie Centrum Kliniczne

🇵🇱

Gda?sk, Poland

Krakowski Szpital Specjalistyczny im sw. Jana Paw?a II

🇵🇱

Kraków, Poland

Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad

🇵🇱

Warszawa, Poland

FSBI Russian Oncology Research Center n.a. Blokhin of MOH RF

🇷🇺

Moscow, Moskovskaja Oblast, Russian Federation

S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)

🇷🇺

Saint-Petersburg, Sankt Petersburg, Russian Federation

Scientific Research Oncology Institute named after N.N. Petrov

🇷🇺

St. Petersburg, Sankt Petersburg, Russian Federation

University Hospital Medical Center Bezanijska kosa

🇷🇸

Belgrade, Serbia

University Clinic Golnik

🇸🇮

Golnik, Slovenia

Medical Oncology Centre of Rosebank

🇿🇦

Johannesburg, South Africa

Eugene Marais Hospital

🇿🇦

Pretoria, South Africa

Corporacio Sanitaria Parc Tauli

🇪🇸

Sabadell, Barcelona, Spain

Hospital Son Llatzer

🇪🇸

Palma de Mallorca, Islas Baleares, Spain

Clinica Universitaria de Navarra

🇪🇸

Pamplona, Navarra, Spain

Hospital de Basurto

🇪🇸

Bilbao, Vizcaya, Spain

Hospital Universitari Vall d'Hebron

🇪🇸

Barcelona, Spain

Hospital Universitario la Fe

🇪🇸

Valencia, Spain

Lungmedicinska kliniken, Centrum för kirurgi, ortopedi och cancervård, Universitetssjukhuset

🇸🇪

Linköping, Sweden

Uni Hospital in Lund

🇸🇪

Lund, Sweden

Karolinska Universitetssjukhuset, Solna

🇸🇪

Solna, Sweden

Uppsala University Hospital

🇸🇪

Uppsala, Sweden

CHUV

🇨🇭

Lausanne, Switzerland

UniversitätsSpital Zürich

🇨🇭

Zürich, Switzerland

Taichung Veterans General Hospital

🇨🇳

Xitun Dist., Taiwan

Chulalongkorn Hospital

🇹🇭

Bangkok, Thailand

Maharaj Nakorn Chiang Mai Hospital

🇹🇭

ChiangMai, Thailand

Chemotherapy SI Dnipropetrovsk MA of MOHU

🇺🇦

Dnipropetrovsk, Ukraine

Queen Elizabeth Hospital

🇬🇧

Birmingham, United Kingdom

The Clatterbridge Cancer Centre NHS Foundation Trust

🇬🇧

Wirral, United Kingdom

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